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The approach to patients with chronic cough has been well defined and evaluated in the literature through a number of prospective studies. Meticulous attention to detail of the afferent loop of the cough reflex has helped identify the cause of cough in most patients. The most common causes appear to be similar in both children and adults and include asthma, postnasal drip syndromes, gastroesophageal reflux diseases, and aspiration. In children, recurrent viral infections and infections with atypical organisms also are very prevalent. Specific therapy directed at the cause alleviates the cough in most patients. In some patients, there may be more than one cause of cough. Invasive testing (eg, bronchoscopy and esophageal pH probing) is rarely necessary. In patients in whom a specific cause cannot be identified or in whom cough modifiers are necessary while specific therapy is taking hold, antitussives of both the narcotic and nonnarcotic variety are helpful.

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A 27-year-old woman presented with cough, fever, and pulmonary infiltrates after heavy cocaine smoking. Large amounts of carbonaceous material and pigment-laden macrophages were recovered by bronchoalveolar lavage. Alveolar deposition of particulate matter from heavy cocaine smoking has not been previously reported and may have been the cause of this patient's symptoms and abnormal findings on chest radiograph.

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A comprehensive program of clinical and administrative strategies to reduce expenditures for antimicrobial agents is described. Clinical intervention strategies include the use of antimicrobial order sheets, standardized dosage regimens, restriction policies for certain antimicrobial agents, and position statements on the use of restricted agents. A cornerstone of the program is the support for cost-reduction interventions offered by the pharmacy and therapeutics committee and its subcommittee on therapeutics; that support is demonstrated through endorsement and enforcement of pharmacy programs. Physicians are reminded of the cost-reduction programs through periodic articles in the pharmacy newsletter and an "antibiogram" card supplied by the division of epidemiology. The effectiveness of these interventions has been demonstrated by progressive decreases in expenditures for antimicrobial agents during 1987 and 1988. Antimicrobial agents also account for increasingly smaller percentages of the total drug budget. This combination of clinical and administrative strategies reduced expenditures for antimicrobial agents by more than $700,000 over two years without the use of clinical specialists or any apparent sacrifice in the quality of patient care.

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Inhalation challenge with methacholine is helpful in establishing the diagnosis of hyperreactive airways disease and its association with cough. It remains a valuable, safe, diagnostic tool. It appears that cough resulting from hyperreactive airways disease is a common clinical disorder that can be treated successfully in nearly all patients. Fifty percent of these patients go on to have more typical signs and symptoms of bronchial asthma over time.

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Bronchial hyperresponsiveness is a constant feature of asthma even when airflow obstruction is absent. Detecting nonspecific bronchial hyperresponsiveness is useful when the diagnosis of asthma has not been confirmed or when a patient describes symptoms of cough, chest tightness, and dyspnea that cannot be ascribed to other causes. Also, because wheezing is a symptom of other disorders, inhalation challenge tests can be useful in defining its cause when reversible airflow obstruction has not been documented. A number of easy and safe techniques are available to detect nonspecific bronchial hyperresponsiveness. The histamine and methacholine challenge have had the most widespread use in the clinical pulmonary function laboratory. The exercise and cold air challenges are limited by expense. The osmotic challenge may gain more acceptance as experience with this technique grows. These different agents have the advantage of simplicity, reproducibility, a low number of adverse effects, and a high degree of specificity and sensitivity. A limited number of asthmatics show bronchial hyperresponsiveness to specific agents such as chemical sensitizers in the workplace, aeroallergens, aspirin, nonsteroidal anti-inflammatory agents, and sulfiting agents. Bronchoprovocation testing with these agents is usually reserved for the hospital laboratory because severe or delayed reactions may occur. These tests, however, can be extremely useful in defining a population of sensitive asthmatics.

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Cough is a complex physiologic event that protects the lungs from mechanical, chemical, and thermal injury. It is a normal reflex and therefore helps humans to adapt to an ever-changing environment. Cough can also be a pathologic reflex in that it may be an important and often the only sign of serious disease, may significantly contribute to the spread of airborne infection, and in some instances, may result in severe functional or structural damage to the organism. This article focuses on the pathophysiology of the afferent limb of the cough reflex, including a discussion of the causes, the diagnostic workup, and the treatment of cough.

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In order to study whether the methacholine inhalation challenge could predict which patients with allergic rhinitis were at risk to develop asthma, we prospectively studied a group of ragweed-sensitive patients over a four to five year period. On the initial study, 16 of 40 patients (40 percent) were found to be hyperresponsive to methacholine. On the follow-up study, three of these 16 patients (19 percent) were found to have developed asthma from one and one-half to five years after the initial testing. Each had greater methacholine responsiveness on repeat study. The degree of methacholine hyperresponsiveness, judged by the PD20, could not predict which of the initial responders would develop asthma. Twenty-four (60 percent) of our patients showed normal responses to methacholine on initial study; none developed asthma and 88 percent remained nonresponders on repeat study. Our study shows that allergic rhinitis patients hyperresponsive to methacholine are at greater risk to develop asthma than those with normal bronchial challenges (p less than 0.05).

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Management of chronic cough is complex and warrants careful evaluation. Some patients cough for years without help because of the indiscriminate use of antitussive medications. All patients should be evaluated in a specific manner. The cause of cough can be found and effectively treated in almost all patients. Antitussive therapy should only be used as adjuvant therapy or when a cause cannot be found and the patient is not harmed by decreasing the cough. When used, the safest, least expensive antitussive drug should be instituted for a limited time pending re-evaluation of the patient's clinical course.

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Cough is a common symptom in the smoking and non-smoking patient seeking medical attention from the office-based physician. Often, a comprehensive history and physical examination suggest the correct diagnosis, and specific therapy can be directed to the underlying disease. A chest roentgenogram is an essential part of the workup; it may suggest tuberculosis, chronic fungal infection, bronchiectasis, or lung abscess. In addition, bronchogenic carcinoma, which is increasing in frequency in the population, has several common manifestations that can be recognized on the chest roentgenogram. Pulmonary function studies are often helpful in the workup of the patient with chronic cough. A pattern of obstructive lung disease is seen with asthma, chronic bronchitis, and bronchiectasis. Diseases that cause lung fibrosis, such as idiopathic pulmonary fibrosis, sarcoidosis, and pneumoconiosis, give a restrictive ventilatory defect. Bronchoprovocation testing can be helpful when baseline pulmonary function tests are normal and the diagnosis of postviral bronchitis or cough-variant asthma is suggested. If the bronchial inhalation challenge is negative, these diagnoses can be excluded. Chronic rhinosinusitis with associated postnasal drip is one of the most common causes of chronic cough and is often difficult to confirm because the physical examination and roentgenogram of the paranasal sinuses may be normal. In a great majority of patients with chronic cough, a diagnosis can be established by simple, clinical and laboratory procedures used in the outpatient setting.

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Because lateral position can be used to locate a pulmonary artery catheter tip in lung regions where venous pressure exceeds alveolar pressure, we studied the effect of lateral position on the correlation between pulmonary artery occlusion pressure (Pw) and left atrial pressure (Pla) at various increments of positive-end expiratory pressure (PEEP). In ten normal anesthetized pigs, catheters were placed in the left atrium and right and left pulmonary arteries; simultaneous measurements of Pla and Pw from both catheters were obtained in the supine, right lateral, and left lateral positions. Pw obtained in the lateral position when the catheter tip was vertically located below the left atrium ("lower") more accurately reflected Pla changes than Pw obtained from catheters above the left atrium, at PEEP levels less than 20 cm H2O. Although most catheter tips were located below the left atrium in the supine position, our data from the lower catheter more accurately assessed Pla than did the Pw obtained in the supine position; this was particularly evident when the catheter tip was located vertically above the left atrium. These findings suggest that the lateral position can be useful in measuring Pw during continuous positive-pressure ventilation. However, further studies in humans are needed before this maneuver can be recommended.

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PEEP may decrease regional perfusion to nondependent lung regions, thereby creating different zones of thermal dissipation in dependent and nondependent zones of the lung. Under these conditions, the measurement of cardiac output by thermodilution may, thus, be influenced by the vertical position of the pulmonary artery catheter in the lung. We investigated this hypothesis in 7 healthy, anesthetized pigs by comparing cardiac output measurements from thermistors located in dependent and nondependent lung regions at varying levels of PEEP. Our data from thermistors in these 2 positions were similar, suggesting that the measurement of cardiac output by thermodilution is not influenced by the vertical position of the thermal sensor with respect to the left atrium.

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Three patients with recurrent emergency room visits and hospitalizations for bronchial asthma are described. Although each patient had respiratory distress associated with wheezing and an apparent response to conventional therapy, other features were inconsistent with the pathophysiology of asthma. These included absence of a significantly elevated alveolar-arterial oxygen tension difference, lack of roentgenographic hyperinflation, and normal small airway function soon after clinical response. Furthermore, bronchial hyperreactivity, a constant feature of asthma, was absent in all patients. Each patient demonstrated wheezing that was self-induced and heard loudest over the neck. Two patients had previous psychiatric illness, one of whom had been hospitalized for factitious fever. We believe that these patients had a form of factitious illness not previously described. Recognition of this syndrome may avoid unnecessary medical care and allow initiation of appropriate psychiatric follow-up.

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Current theories of cough have been reviewed and related to the pathophysiology of bronchial asthma. The cough reflex arc and its association with the phenomenon of bronchial hyperreactivity have been stressed. A review of the recent literature suggests that bronchodilator therapy will modify this reflex and eliminate cough in most patients. The mechanism of action of bronchodilators may be associated with modification of bronchial hyperreactivity.

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To help in clarifying the conflicting data on the role of tracheobronchial microflora in chronic bronchitis, the tracheobronchial microflora of a homogeneous group of clinically stable patients with chronic obstructive bronchitis was characterized by transtracheal aspiration. Their mean percentage ratio of forced expiratory volume in 1 sec to the forced vital capacity was 45%. The results were that (1) a bacterial tracheobronchial microflora was present in only 50% of the patients, (2) viridans streptococci were the bacteria most frequently isolated, and (3) the presence or absence of a tracheobronchial microflora was significantly associated with the amount of present cigarette smoking. The fact that patients who smoke less than one pack per day were most likely to have a sterile tracheobronchial tree (P=0.015) implied that there was a critical amount of cigarette smoke that impaired the clearance and/or detoxification of bacteria from the tracheobronchial tree and that it must have been persistently present.

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Cough, dyspnea, and chest pain are symptoms common to many cardiopulmonary diseases. A comprehensive evaluation, including a history, physical examination, ECG, chest roentgenogram, and pulmonary function studies, will often yield a specific diagnosis. However, when these symptoms are intermittent, as they often are in patients with bronchial asthma, the diagnosis may not be apparent. If asthma is thought to be a diagnostic possibility, a bronchial inhalation challenge should be used to demonstrate bronchial hyperreactivity, the hallmark of asthma. The methacholine chloride inhalation challenge is a simple and useful laboratory test to diagnose bronchial hyperreactivity. We describe eight patients with a variety of clinical symptoms to demonstrate the usefulness of this test. Patients with unexplained respiratory symptoms should be considered for bronchial inhalation challenge before proceeding to more invasive diagnostic procedures.

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To determine the relative cultural accuracy of transtracheal aspiration (TTA), wire-brushing under direct vision through a flexible fiberoptic bronchoscope (WBB), and expectorated sputum (ES) in localized pulmonary infections, we compared each method with percutaneous needle lung aspiration (PLA) cultures in patients with peripheral lung abscesses. Of the 27 organisms that PLA cultures isolated from ten lung abscesses (eight aerobic, two anaerobic), TTA identified 81 percent plus an additional five, and WBB 68 percent plus 16. Of the 14 organisms that PLA cultures isolated from eight aerobic abscesses, TTA identified 93 percent plus an additional two, WBB 83 percent plus 12, and ES 71 percent plus 19. From a laboratory standpoint, we concluded the following: (1) when PLA cultures cannot be obtained, the most accurate method for determining the cause of a localized pulmonary infection is TTA generates false-negative and false-positive information, it may not be an appropriate standard to evaluate other methods, such as ES.

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Using a diagnostic protocol based on the anatomy and distribution of cough receptors and afferent nerves, we sought to determine the causes and outcome of specific therapy of chronic persistent cough in 49 consecutive and unselected patients. A specific diagnosis was made in all. Cough was due to chronic postnasal dip from a variety of conditions in 29%, asthma in 25%, postnasal drip plus asthma in 18%, chronic bronchitis in 12%, gastroesophageal reflux in 10%, and miscellaneous disorders in 6%. History, physical examination, and methacholine inhalational challenge diagnosed disease in 86% of all patients. Adjusted success rates for specific therapy, and average of 4.4 and 18.9 months after therapy had been prescribed, were 98% and 97%, respectively. We concluded the following about chronic persistent cough; using an anatomic, diagnostic protocol, the cause can be consistently determined; postnasal drip and/or bronchial asthma are very common causes of cough; the outcome of specific therapy, almost without exception, is successful and sustained.

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